Repeated recall of learned immunosuppression: evidence from rats and men

Akin to other physiological responses, the immune system can be modified, via Pavlovian or behavioral conditioning. It is unknown, however, whether and to what extent learned immune responses can be repeatedly recalled over time. Here we demonstrate in both rats and humans that repeated contingent pairing of a novel taste (conditioned stimulus, CS) together with the immunosuppressive drug cyclosporine A as unconditioned stimulus (US) leads to the acquisition of a learned immunosuppression. Sole presentation of the CS caused a significant inhibition of interleukin (IL)-2 and interferon (IFN)-γ production by rat splenic T cells and human peripheral T lymphocytes, closely mimicking the effect of the drug. More importantly, a comparable suppression of cytokine production was also observed after a second, unreinforced exposure to the CS that was separated from the first evocation by an interval of 6 (rats) or 11 (humans)days, respectively. Together, our findings demonstrate that a learned immunosuppression can be repeatedly recalled in both animals and humans, which is an important prerequisite for the implementation of conditioning paradigms as supportive therapy.